Bibliometric analysis of PTEN in neurodevelopment and neurodegeneration.

Phosphatase and tensin homologue deleted on chromosome ten (PTEN) was initially recognized as a significant regulator of cancer suppression and could impede cancer cell survival, proliferation, and energy metabolism. PTEN is highly expressed in neurons and performs crucial functions in neurogenesis, synaptogenesis, and neuronal survival. Disruption of PTEN activity may also result in abnormal neuronal function and is associated with various neurological disorders, including stroke, seizures, and autism. Although several studies have shown that PTEN is involved in the development and degenerative processes of the nervous system, there is still a lack of in-depth studies that summarize and analyse patterns of cooperation between authors, institutions, countries, and journals, as well as research hotspots and trends in this important field. To identify and further visualize the cooperation and comprehend the development and trends of PTEN in the nervous system, especially in neural development and neurological diseases, we used a bibliometric analysis to identify relevant publications on this topic. We first found that the number of publications displayed a growing trend with time, but this was not stable. Universities, institutions, and authors from the United States are leading in this area of research. In addition, many cutting-edge research results have been discovered, such as key regulatory molecules and cellular mechanisms of PTEN in the nervous system, which may provide novel intervention targets and precise therapeutic strategies for related pathological injuries and diseases. Finally, the literature published within the last 5 years is discussed to identify future research trends regarding PTEN in the nervous system. Taken together, our findings, analysed using bibliometrics, may reflect research hotspots and trends, providing a reference for studying PTEN in the nervous system, especially in neural development and neurological diseases. These findings can assist new researchers in developing their research interests and gaining basic information. Moreover, our findings also may provide precise clinical guidelines and strategies for treating nervous system injuries and diseases caused by PTEN dysfunction.

A bibliometric analysis of hotpots and trends for the relationship between skin inflammation and regeneration.

Background: Skin regeneration is a challenging issue worldwide. Increasing research has highlighted the role of immune cells in healing and the underlying regulatory mechanism. The purpose of this study was to identify the hotspots and trends in skin regeneration and inflammation research through bibliometrics and to provide insights into the future development of fundamental research and disease treatment. Methods: Publications were collected from the Web of Science Core Collection on March 1, 2022. Articles and reviews published in English from January 1, 1999, to December 31, 2022, were selected, and statistical analyses of countries, institutions, authors, references, and keywords were performed using VOSviewer 1.6.18 and CiteSpace 5.8. Results: A total of 3,894 articles and reviews were selected. The number of publications on skin inflammation and regeneration showed an increasing trend over time. Additionally, authors and institutions in the United States, United Kingdom, Canada, and China appeared to be at the forefront of research in the field of skin inflammation and regeneration. Werner Sabine published some of the most cited papers. Wound Repair and Regeneration was the most productive journal, while Journal of Investigative Dermatology was the most cited journal. Angiogenesis, diamonds, collagen, cytokine, and keratinocytes were the five most commonly used keywords. Conclusion: The number of publications on skin inflammation and regeneration show an increasing trend. Moreover, a series of advanced technologies and treatments for skin regeneration, such as exosomes, hydrogels, and wound dressings, are emerging, which will provide precise information for the treatment of skin wounds. This study can enhance our understanding of current hotspots and future trends in skin inflammation and regeneration research, as well as provide guidelines for fundamental research and clinical treatment.

[Epidemiological Characteristics and Drug Resistance of Microbial Pathogens of Patients With Silicosis Combined With Pulmonary Infection].

Objective: To investigate the epidemiological characteristics of patients with silicosis combined with pulmonary infection in recent years, to study the distribution and the drug susceptibility of fungal and bacterial pathogens in their sputum samples, and to provide references for the prevention and treatment of silicosis and the appropriate drug use. Methods: The clinical data and drug sensitivity test results of patients with silicosis combined with pulmonary infection diagnosed at the Department of Occupational Diseases, West China Fourth Hospital, Sichuan University were retrospectively analyzed. Results: A total of 318 patients with silicosis combined with pulmonary infection who received treatment between January 2017 and December 2020 were enrolled. All the patients had positive microorganism test results. All participants were male. Their median age at the time of onset was 51.00 years and the median time of exposure to silica dust at work was 12.40 years. They worked mostly in construction, non-ferrous metal mining, and coal mining. The main types of work they did were pneumatic drilling, coal digging, and mining. The positive detection rates for the first, second and third phases of silicosis were 27.54%, 28.32%, and 32.97%, respectively. A total of 341 strains of fungal and bacterial pathogens were isolated, of which, 54.1% were fungi, including 114 strains (35.8%) of Candida albicans, and 53.1% were bacteria, including 168 strains (52.8%) of gram-negative bacteria, most of which being Klebsiella pneumoniae (30.2%). There was only 1 strain (0.3%) of gram-positive bacteria, namely Staphylococcus hemolyticus. Gram-negative bacilli were most resistant to ampicillin and highly sensitive to penicillin G and ofloxacin. Conclusion: Among patients with silicosis combined with pulmonary infection, the incidence of pulmonary infection increases along with the progress of silicosis. Microorganism analysis reveals high detection rates for fungi and the bacteria detected are predominantly gram-negative bacteria. The overall prospect for drug resistance rate was not optimistic.

A bibliometric analysis of apoptosis in glaucoma.

Background: Glaucoma is the first irreversible and second blindness disease, which is characterized by the death of retinal ganglion cells (RGCs) and degeneration of the optic nerve. Previous works have indicated that apoptosis is the main reason for RGC death in glaucoma. Although many studies have investigated the mechanism of apoptosis and different strategies targeting apoptosis to protect the RGCs and finally recover the impaired vision in the glaucoma. However, the global trend and hotspots of apoptosis in glaucoma have not been well illustrated and discussed. Methods: Documents were extracted from the Web of Science Core Collection on November 2, 2022. We selected articles and reviews published in English from January 1, 1999 to November 1, 2022 to perform visual analysis and statistical analysis of countries, institutions, authors, references and keywords by VOSviewer 1.6.18 and CiteSpace 5.8. Results: The publications about apoptosis in glaucoma show an increasing trend over time. Besides, the authors, institutions in the US and China published the most numbers of articles with the highest citation, which may be leading the research in the field of apoptosis in glaucoma. Last, series of advanced research results, technology and treatment for glaucoma, such as the discovery of key regulatory mechanisms on RGC apoptosis are emerging and will provide precise strategies for the treatment of glaucoma. Conclusion: This research will broaden our comprehension about the role of apoptosis in the process of glaucoma, and provide guidelines for us in basic research and disease treatment in the further.

The Na+/H+ antiporter GbSOS1 interacts with SIP5 and regulates salt tolerance in Gossypium barbadense.

Cotton is a globally cultivated economic crop and is a major source of natural fiber and edible oil. However, cotton production is severely affected by salt stress. Although Salt Overly Sensitive 1 (SOS1) is a well-studied Na+/H+ antiporter in multiple plant species, little is known about its function and regulatory mechanism in cotton. Here, we cloned a salt-induced SOS1 from sea-island cotton. Real-time quantitative PCR analysis revealed that GbSOS1 was induced by multiple stresses and phytohormones. Silencing GbSOS1 through virus-induced gene silencing significantly reduced cotton resistance to high Na+ but mildly affected Li+ tolerance. On the other hand, overexpression of GbSOS1 enhanced salt tolerance in yeast, Arabidopsis, and cotton largely due to the ability to maintain Na+ homeostasis in protoplasts. Yeast-two-hybrid assays and bimolecular fluorescence complementation identified a novel protein interacting with GbSOS1 on the plasma membrane, which we named SOS Interaction Protein 5 (SIP5). We found that the SIP5 gene encoded an unknown protein localized on the cell membrane. Silencing SIP5 significantly increased cotton tolerance to salt, exhibited by less wilting and plant death under salt stress. Our results revealed that GbSOS1 is crucial for cotton survival in saline soil, and SIP5 is a potentially negative regulator of SOS1-mediated salt tolerance in cotton. Overall, this study provides a theoretical basis for elucidating the molecular mechanism of SOS1, and a candidate gene for breeding salt-tolerant crops.

Physical activity levels of children and adolescents with intellectual disabilities in Northern China.

BACKGROUND: Limited research has looked at the physical activity (PA) among Chinese children and adolescents with intellectual disabilities. METHODS: The Children's Leisure Activities Study Survey-Chinese version was applied in evaluating PA levels among children and adolescents with intellectual disabilities. RESULTS: The data indicated that only 29.5% of children and adolescents with intellectual disabilities met the PA recommendation. Boys engaged in significantly more MVPA and had higher energy expenditure than girls during weekdays and the whole week. The general trend in PA levels demonstrated a downtrend with the growth of age of children and adolescents with intellectual disabilities. The students aged 6-12 years old performed more MVPA and had greater energy expenditure compared with those 13-15 and 16-18 years old. CONCLUSION: The level of PA among Chinese children and youths with intellectual disabilities is remarkably low, and there is a large gap compared with the PA recommendation.

["Acupuncture network drug"--transformation and application strategies of exosomes based on characteristics of network regulation of acupuncture therapy].

Although the basic mechanism of acupuncture-moxibustion has been revealed from many aspects, there are still many shackles in the transformation of the related research achievements. The transformation of academic achievements of experimental acupunctology is an urgent issue to be solved at present. Network regulation is the basic action mode of acupuncture therapy. In the present paper, we proposed that the "acupuncture network drug" could carry a variety of effective active ingredients which may be the core component of network regulation of acupuncture therapy. The "exosomes", polyvesicle derived from the intracellular lysosomal microparticles invagination, contain complex RNAs and proteins and exist in the body fluids and function in secreting abundant activate substances to participate in intercellular communication, which is the research hotspot in the field of frontier life science in the world. They play an important role in the diagnosis and treatment of diseases, and drug development, etc.. Our studies using rats with adjuvant arthritis and mice with sepsis displayed that after intraperitoneal administration of serum exosomes derived from normal animals receiving acupuncture intervention, an acupuncture-like analgesic effect and an anti-inflammatory effect were achieved, respectively. It is thus possible that acupuncture network drugs could be developed from serum exosomes secreted by exosome autogenous living cells after acupuncture intervention by virtue of the characteristics of low immunogenicity and may have great advantages in drug development and modification. It is also expected to provide new ideas for the transformation of experimental research results and to in depth give explanations about the underlying mechanisms of acupuncture therapy.

[Clinical characteristics and gene variants of patients with infantile intrahepatic cholestasis].

OBJECTIVE: To explore the clinical characteristics and genetic findings of patients with infantile intrahepatic cholestasis. METHODS: The clinical data were collected in children who were admitted to the Department of Gastroenterology in Children's Hospital, Capital Institute of Pediatrics from June 2017 to June 2019 and were suspected of inherited metabolic diseases. Next generation sequencing based on target gene panel was used for gene analysis in these children. Sanger sequencing technology was used to verify the genes of the members in this family. RESULTS: Forty patients were enrolled. Pathogenic gene variants were identified in 13 patients (32%), including SLC25A13 gene variation in 3 patients who were diagnosed with citrin deficiency, JAG1 gene variation in 3 patients who were diagnosed with Alagille syndrome, ABCB11 gene variation in 3 patients who were diagnosed with progressive familial intrahepatic cholestasis type 2, HSD3B7 gene variation in 1 patient who was diagnosed with congenital bile acid synthesis defect type 1, AKR1D1 gene variation in 1 patient who was diagnosed with congenital bile acid synthesis defect type 1, NPC1 gene variation in 1 patient who was diagnosed with Niemann-Pick disease, and CFTR gene variation in 1 patient who was diagnosed with cystic fibrosis. CONCLUSIONS: The etiology of infantile intrahepatic cholestasis is complex. Next generation sequencing is helpful in the diagnosis of infantile intrahepatic cholestasis.

The effectiveness of cupping therapy on chronic fatigue syndrome: A single-blind randomized controlled trial.

BACKGROUND: and purpose: We investigated the effectiveness of cupping therapy with three different pressures in patients with chronic fatigue syndrome (CFS). MATERIALS AND METHODS: The participants were randomly assigned to three groups, as follows: cupping pressure of -0.02 mpa (n = 38), -0.03 mpa (n = 38), or -0.05 mpa (n = 36). Each group received cupping treatment that consisted of 10 sessions over 5 weeks (2 sessions per week). The primary outcomes were Fatigue Scale (FS-14) score and Fatigue Assessment Instrument (FAI) score after 5 and 10 sessions. The secondary outcomes were the Self-Rating Anxiety Scale (SAS) score, the Self-Rating Depression Scale (SDS) score, and the Pittsburgh Sleep Quality Index (PSQI) score. RESULTS: There were 91 participants who completed the trial. After five sessions of treatment, the primary outcome of FS-14 score decreased by 3.20 (2.19, 4.21) in the -0.02 mpa group, by 2.39 (1.51, 3.27) in the -0.03 mpa group, and by 3.40 (2.28, 4.52) in the -0.05 mpa group (P = 0.667). After 10 sessions of treatment, the outcome of FS-14 score decreased by 5.00 (3.79, 6.21) in the -0.02 mpa group, by 4.06 (3.07, 5.05) in the -0.03 mpa group, and by 4.77 (3.52, 5.94) in the -0.05 mpa group (P = 0.929). And, the results were statistically different between 5 sessions and 10 sessions of treatment (P < 0.01). However, there were no statistical differences in FAI, SAS, SDS, and PSQI scores between the three groups after 5 sessions and 10 sessions of treatment. CONCLUSIONS: In conclusion, cupping therapy has significantly relieved fatigue symptoms and improved emotion and sleep condition of CFS patients, and 10 sessions of treatment had superior results compared with 5 sessions in each group. Moreover, in 5 sessions of treatment, cupping with high pressure showed better improvement in fatigue syndromes and sleep condition according to effective rates. TRIAL REGISTRATION: Chinese clinical trial registry (ChiCTR1800017590); Ethical approval number: ChiECRCT-20180085.

YiQiFuMai Lyophilized Injection ameliorates tPA-induced hemorrhagic transformation by inhibiting cytoskeletal rearrangement associated with ROCK1 and NF-κB signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Thrombolytic therapy with tissue plasminogen activator (tPA) after ischemic stroke exacerbates blood-brain barrier (BBB) breakdown and leads to hemorrhagic transformation (HT). YiQiFuMai Lyophilized Injection (YQFM) is a modern preparation derived from Sheng-mai San (a traditional Chinese medicine). YQFM attenuates the BBB dysfunction induced by cerebral ischemia-reperfusion injury. However, whether YQFM can suppress tPA-induced HT remains unknown. AIM OF THE STUDY: We investigated the therapeutic effect of YQFM on tPA-induced HT and explored the underlying mechanisms in vivo and in vitro to improve the safety of tPA use against stroke. METHODS: Male C57BL/6J mice were subjected to 45 min of ischemia and 24 h of reperfusion. tPA (10 mg/kg) were infused 2 h after occlusion and YQFM (0.671 g/kg) was injected 2.5 h after occlusion. The in vitro effect of YQFM (100, 200, 400 µg/mL) on tPA (60 µg/mL)-induced dysfunction of the microvascular endothelial barrier in the brain following oxygen-glucose deprivation/reoxygenation (OGD/R) was observed in bEnd.3 cells. RESULTS: YQFM suppressed tPA-induced high hemoglobin level in the brain, mortality, neurologic severity score, BBB permeability, expression and activation of matrix metalloproteinase (MMP)-9 and MMP-2, and degradation of tight-junction proteins. Furthermore, YQFM significantly blocked tPA-induced brain microvascular endothelial permeability and phosphorylation of Rho-associated kinase (ROCK)1, myosin light chain (MLC), cofilin and p65 in vivo and in vitro. CONCLUSION: YQFM suppressed tPA-induced HT by inhibiting cytoskeletal rearrangement linked with ROCK-cofilin/MLC pathways and inhibiting the nuclear factor-kappa B pathway to ameliorate BBB damage caused by tPA.

Transcriptomic analysis of Bursaphelenchus xylophilus treated by a potential phytonematicide, punicalagin.

Punicalagin showed significant nematotoxic activity against pine wood nematode (PWN), Bursaphelenchus xylophilus, in the authors' previous research. The authors performed high-throughput transcriptomic sequencing of punicalagin-treated nematodes to generate clues for its nematotoxic mechanism of action. The authors identified 2,575 differentially expressed genes, 1,428 of which were up-regulated and 1,147 down-regulated. Based on a comprehensive functional in silico analysis, the authors speculate that PWN may respond to the stimulus of punicalagin through phagosome, endocytosis, peroxisome and MAPK signaling pathways. In addition, punicalagin could greatly affect PWN energy metabolism including oxidative phosphorylation. The genes encoding twitchin and a nematode cuticular collagen could be crucial regulation targets of punicalagin, which might contribute to its nematotoxic activity against PWN.Punicalagin showed significant nematotoxic activity against pine wood nematode (PWN), Bursaphelenchus xylophilus, in the authors' previous research. The authors performed high-throughput transcriptomic sequencing of punicalagin-treated nematodes to generate clues for its nematotoxic mechanism of action. The authors identified 2,575 differentially expressed genes, 1,428 of which were up-regulated and 1,147 down-regulated. Based on a comprehensive functional in silico analysis, the authors speculate that PWN may respond to the stimulus of punicalagin through phagosome, endocytosis, peroxisome and MAPK signaling pathways. In addition, punicalagin could greatly affect PWN energy metabolism including oxidative phosphorylation. The genes encoding twitchin and a nematode cuticular collagen could be crucial regulation targets of punicalagin, which might contribute to its nematotoxic activity against PWN.

Design, synthesis and antineoplastic activity of novel 20(S)-acylthiourea derivatives of camptothecin.

For the purpose of advancing our research on diverse C-20 decorated derivatives of camptothecin (CPT), 46 new CPT acylthiourea derivatives were synthesized and evaluated in vitro for their cytotoxicity. All the compounds showed promising in vitro cytotoxicity against six tumor cell lines (Hep3B, MCF7, A549, MDA-MB-231, KB and KB-vin). Out of them, compound c20 possesses remarkable in vitro cytotoxic activity and is more potent than topotecan. Mechanistically, c20 not only induces cell cycle arrest and cell apoptosis in A549 cells, but also inhibits Topo I activity in the cell and cell-free system in a manner similar to that of topotecan. In both xenograft and primary HCC mouse models, c20 displays significant in vivo anti-cancer activity and is more potent than topotecan. In addition, the acute toxicity assay showed that c20 has no apparent toxicity to mouse liver, kidney and hemopoietic system of the FVB/N mice. Take together, these results indicated that compound c20 could be a potential anti-cancer candidate for further clinical trial.

[Detection of viral pathogens and allergens in infants and young children at high risk of asthma during a wheezing episode].

OBJECTIVE: To investigate the viral etiology and allergen distribution in infants and young children at high risk of asthma during a wheezing episode. METHODS: A total of 135 infants and young children at high risk of asthma were enrolled who were admitted due to asthmatic bronchitis or asthmatic bronchopneumonia between April 2016 and August 2017. Fluorescent probe PCR was used to measure influenza A (Flu A), respiratory syncytium virus (RSV), adenovirus (ADV), parainfluenza virus (PinF), human rhinovirus (HRV), human partial lung virus (hMPV) and human bocavirus (HBoV) in nasopharyngeal aspirates. ImmunoCAP was used to measure inhaled allergens, food allergens, and total IgE concentration. RESULTS: Among the 135 patients, the overall virus detection rate of nasopharyngeal aspirates was 49.6%, and HRV had the highest detection rate of 25.2%, followed by HBoV (9.6%), RSV (8.1%), PinF (5.9%), Flu-A (3.7%), ADV (1.5%) and hMPV (0.7%). The 1-3 years group had a significantly higher detection rate of HRV than the <1 year group (P<0.05). The positive rate of allergen screening was 59.3%, with 44% for inhaled allergens and 89% for food allergens. Among the inhaled allergens, dust mites had the highest positive rate of 77%, followed by mould (37%), pollen (26%) and animal dander (9%). Among the food allergens, egg white had a positive rate of 73% and milk had a positive rate of 68%. The <1 year group had a significantly higher positive rate of inhaled allergens than the 1-3 years group (P<0.05). The 1-3 years age group had a significantly higher level of T-IgE than the <1 year group (P<0.05). The positive virus group had a significantly higher positive rate of inhaled allergens than the non-virus group (P<0.05). The children with the second wheezing episode had significantly higher positive rates of inhaled allergens and food allergens and level of T-IgE than those with the first wheezing episode (P<0.05). The children with the second wheezing episode also had significantly higher positive rates of dust mites and mould than those with the first wheezing episode (P<0.05). CONCLUSIONS: Early HRV infection and inhaled allergen sensitization are closely associated with the development of wheezing in infants and young children at high risk of asthma.

The role of miR-29c/B7-H3/Th17 axis in children with Mycoplasma pneumoniae pneumonia.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is one of the most common causes of community-acquired pneumonia in children. Recent studies demonstrated that the incidence of severe or fatal M. pneumoniae was gradually increasing, which may be related to the excessive inflammation. However, the exact pathogenesis of excessive inflammation in Mycoplasma pneumoniae pneumonia(MPP) is still unclear. This study aimed to reveal the role of miR-29c/B7-H3/Th17 axis in children with MPP. METHODS: Children hospitalized in Respiratory Department during Jan. 2014 to Dec. 2015 were enrolled. All children enrolled was confirmed with MP infection using real-time PCR and ELISA. Children were excluded if they were co-infected with other pathogens. A total of 52 children with MPP and 26 controls were enrolled. miR-29c expression in monocytes of children with MPP was determined by real-time PCR and soluble B7-H3 (sB7-H3) and IL-17 were determined by ELISA, and explore their clinical significance. miR-29c overexpression and silencing technology and luciferase reporter assay were performed to confirm whether B7-H3 is the direct target of miR-29c. The levels of transcription factor ROR-γt in CD4+ T cells and cytokine IL-17A in supernatant were detected after stimulated by different concentrations of B7-H3 fusion protein in vitro. RESULTS: Of all 52 children with MPP, the mean age of the children were 77 ± 33 months, and 23 cases were male accounting for 44.2%. Nineteen cases had pleural effusion accounting for 36.5%. Children with MPP had significantly lower level of miR-29c and higher level of sB7-H3 and IL-17 compared to controls (both P < 0.05). The level of miR-29c significantly increased during convalescent phase compared to that of acute phase while sB7-H3 and IL-17 significantly decreased during convalescent phase (both P < 0.05). There was a positive correlation between the level of sB7-H3 and IL-17 in children with MPP during acute-stage (r = 0.361,P = 0.009). Children with MPP combined with pleural effusion had significantly higher level of sB7-H3 compared to those without pleural effusion (9952.3 ± 3065.3 vs. 7449.7 ± 2231.5, pg/ml), and the levels of sB7-H3 was positively correlated with the number of days of fever. The level of miR-29c was negatively correlated with M. pneumoniae specific IgG, IgM level. High concentrations of B7-H3(15µg/ml) could enhance ROR-γt expression and increase IL-17A. Functional studies based on luciferase reporter assay and immunofluorescence staining suggested that B7-H3 is the direct target of miR-29c, and miR-29c silencing or overexpression could up- or down-regulate the expression of B7-H3 in THP-1 cells. CONCLUSIONS: The axis of miR-29c/B7-H3/Th17 plays a vital role in children with MPP through excessive inflammation. miR-29c and B7-H3 may be the new target for the prevention and treatment of MPP, and may be the novel and potential biomarkers for the assessment of prognosis.

Quantized spin pump on helical edge states of a topological insulator.

We report a theoretical study of the quantized spin pump in a traditional quantum pump device that is based on the helical edge states of a quantum spin Hall insulator. By introducing two time-dependent magnetizations out of phase as the pumping parameters, we found that when the Fermi energy resides in the energy gap opened by magnetization, an integer number of charges or spins can be pumped out in a pumping cycle and ascribed to the possible topological interface state born in between the two pumping potentials. The quantized pump current can be fully spin-polarized, spin-unpolarized, or pure spin current while its direction can be abruptly reversed by some system parameters such as the pumping phase and local gate voltage. Our findings may shed light on generation of a quantized spin pump.

Prognostic effect of adjuvant chemoradiotherapy for patients with gastric cancer: an updated evidence of randomized controlled trials.

The prognostic effect of chemoradiotherapy in gastric cancer has been evaluated for decades while the results are still in debate and heterogeneous. We thus comprehensively updated the evidence through systematic review and meta-analysis to evaluate chemoradiotherapy in gastric cancer to determine its effect. Pubmed, EMBASE, and Cochrane Library from the earliest possible year to April 2017 were searched. Randomised controlled trials (RCTs) that assessed the effects of combined chemoradiotherapy for patients with gastric cancer compared with that of single chemotherapy were included. The main outcome measure was 5-year overall survival (OS) and the second was disease-free survival (DFS) or recurrence-free survival (RFS). Fifteen RCTs involving 3347 patients were included into this meta-analysis. Compared with single chemotherapy, the relative risk (RR) for 5-year OS for chemoradiotherapy was 1.05 (95% CI 0.88 to 1.25), with moderate heterogeneity across eligible trials (I2 = 55.7%, p = 0.016). Subgroup analyses and sensitivity analyses confirmed the consistent findings. We found that significant survival benefit for 5-year DFS/RFS for chemoradiotherapy over single chemotherapy (RR 0.89 95% CI 0.81 to 0.98) for patients with gastric cancer. This updated meta-analysis does not provide strong evidence for a 5-year survival benefit of chemoradiotherapy over chemotherapy alone in patients with gastric cancer. A clear advantage of chemoradiotherapy over chemotherapy has not been established. Further larger RCTs should be conducted to determine its true effect.

Design, semisynthesis and potent cytotoxic activity of novel 10-fluorocamptothecin derivatives.

Fluorination is a well-known strategy for improving the bioavailability of bioactive molecules in the lead optimization phase of drug discovery projects. In an attempt to improve the antitumor activity of camptothecins (CPTs), novel 10-fluoro-CPT derivatives were designed, synthesized and evaluated for cytotoxicity against five human cancer cell lines (A-549, MDA-MB-231, KB, KB-VIN and MCF-7). All of the derivatives showed more potent in vitro cytotoxic activity than the clinical CPT-derived drug irinotecan against the tumor cell lines tested, and most of them showed comparable or superior potency to topotecan. Remarkably, compounds 16b (IC50, 67.0nM) and 19b (IC50, 99.2nM) displayed the highest cytotoxicity against the multidrug-resistant (MDR) KB-VIN cell line and merit further development as preclinical drug candidates for treating cancer, including MDR phenotype. Our study suggested that incorporation of a fluorine atom into position 10 of CPT is an effective method for discovering new potent CPT derivatives.

Production and Partial Characterization of an Alkaline Xylanase from a Novel Fungus Cladosporium oxysporum.

A new fungus Cladosporium oxysporum GQ-3 producing extracellular xylanase was isolated from decaying agricultural waste and identified based on the morphology and comparison of internal transcribed spacer (ITS) rDNA gene sequence. C. oxysporum produced maximum xylanase activity of 55.92 U/mL with wheat bran as a substrate and NH4Cl as a nitrogen source. Mg(2+) improved C. oxysporum xylanase production. Partially purified xylanase exhibited maximum activity at 50°C and pH 8.0, respectively, and showed the stable activity after 2-h treatment in pH 7.0-8.5 or below 55°C. Mg(2+) enhanced the xylanase activity by 2% while Cu(2+) had the highest inhibition ratio of 57.9%. Furthermore, C. oxysporum xylanase was resistant to most of tested neutral and alkaline proteases. Our findings indicated that Cladosporium oxysporum GQ-3 was a novel xylanase producer, which could be used in the textile processes or paper/feed industries.

Jungermannenone A and B induce ROS- and cell cycle-dependent apoptosis in prostate cancer cells in vitro.

AIM: Jungermannenone A and B (JA, JB) are new ent-kaurane diterpenoids isolated from Chinese liverwort Jungermannia fauriana, which show anti-proliferation activities in cancer cells. In this study we investigated the mechanisms underlying the anticancer action of JA and JB in PC3 human prostate cancer cells in vitro. METHODS: A panel of 9 human cancer cell lines was tested. Cell proliferation was assessed with a real-time cell analyzer and MTT assay. Cell apoptosis, cell cycle distribution and ROS levels were measured using cytometry. Mitochondrial damage was examined by transmission electron microscopy. DNA damage was detected with comet assay. Apoptotic, DNA damage- and cell cycle-related proteins were analyzed using Western blotting. The expression of DNA repair genes was measured with qRT-PCR. RESULTS: Both JA and JB exerted potent anti-proliferative action against the 9 cancer cell lines, and PC3 cells were more sensitive with IC50 values of 1.34±0.09 and 4.93±0.20 µmol/L, respectively. JA (1.5 µmol/L) and JB (5 µmol/L) induced PC3 cell apoptosis, which was attenuated by the caspase inhibitor Z-VAD. Furthermore, both JA and JB caused mitochondrial damage and ROS accumulation in PC3 cells, whereas vitamin C blocked the ROS accumulation and attenuated the cytotoxicity of JA and JB. Moreover, both JA and JB induced DNA damage, accompanied by downregulated DNA repair proteins Ku70/Ku80 and RDA51. JA induced marked cell cycle arrest at the G0/G1 phase, which was related to c-Myc suppression, whereas JB enforced the cell cycle blockade in the G2/M phase, which associated with activation of the JNK signaling. CONCLUSION: Both JA and JB induce prostate cancer apoptosis via ROS accumulation and induction of cell cycle arrest.

Design, synthesis, cytotoxic activity and molecular docking studies of new 20(S)-sulfonylamidine camptothecin derivatives.

In an ongoing investigation of 20-sulfonylamidine derivatives (9, YQL-9a) of camptothecin (1) as potential anticancer agents directly and selectively inhibiting topoisomerase (Topo) I, the sulfonylamidine pharmacophore was held constant, and a camptothecin derivatives with various substitution patterns were synthesized. The new compounds were evaluated for antiproliferative activity against three human tumor cell lines, A-549, KB, and multidrug resistant (MDR) KB subline (KBvin). Several analogs showed comparable or superior antiproliferative activity compared to the clinically prescribed 1 and irinotecan (3). Significantly, the 20-sulfonylamidine derivatives exhibited comparable cytotoxicity against KBvin, while 1 and 3 were less active against this cell line. Among them, compound 15c displayed much better cytotoxic activity than the controls 1, 3, and 9. Novel key structural features related to the antiproliferative activities were identified by structure-activity relationship (SAR) analysis. In a molecular docking model, compounds 9 and 15c interacted with Topo I-DNA through a different binding mode from 1 and 3. The sulfonylamidine side chains of 9 and 15c could likely form direct hydrogen bonds with Topo I, while hydrophobic interaction with Topo I and π-π stacking with double strand DNA were also confirmed as binding driving forces. The results from docking models were consistent with the SAR conclusions. The introduction of bulky substituents at the 20-position contributed to the altered binding mode of the compound by allowing them to form new interactions with Topo I residues. The information obtained in this study will be helpful for the design of new derivatives of 1 with most promising anticancer activity.